| 摘要: |
| 目的 制备pH敏感融合膜（MP）包覆的载多柔比星（Dox）的中空介孔二氧化锰（H-MnO2）纳米粒（MP@H-MnO2-Dox纳米粒），并在体外对其进行初步评价。方法 以固体实心二氧化硅为模板，用碱刻蚀的方法合成H-MnO2，制备载Dox的H-MnO2（H-MnO2-Dox），进行MP的包覆构建MP@H-MnO2-Dox纳米粒。对上述仿生纳米体系进行粒径、载药量、MP包覆载体比例的考察，用三（4，7-联苯-1，10-邻菲啰啉）二氯化钌（RDPP）探针进行产氧能力的评价，透析法考察药物体外释放，激光扫描共聚焦显微镜考察其胞内摄取分布情况。结果 成功制备了H-MnO2，其载药率和包封率分别为（79.0±8.7）%和（75.1±7.5）%，MP与H-MnO2质量比为1∶1时能较好地包裹H-MnO2。MP@H-MnO2-Dox粒径为（178.0±9.5）nm，RDPP测定结果显示H-MnO2具有优越的产氧能力。体外药物释放结果显示，MP可以延缓Dox的释放，24 h时MP@H-MnO2-Dox（pH=6.5）的Dox累计释放量低于H-MnO2-Dox（pH=6.5）[（42.0±5.1）% vs（60.0±3.7）%]。胞内摄取分布实验结果显示MP@H-MnO2-Dox纳米粒在pH=6.5条件下具有很强的细胞摄取能力。结论 成功构建了MP@H-MnO2-Dox纳米粒，该仿生纳米体系有望成为缓解缺氧并靶向乳腺癌的多功能药物递送载体。 |
| 关键词: 缺氧 化学治疗 仿生纳米粒 乳腺肿瘤 靶向治疗 |
| DOI：10.16781/j.0258-879x.2021.12.1362 |
| 投稿时间：2021-03-19 |
| 基金项目:国家自然科学基金（81972891），国家临床重点专科-临床药学军队建设项目，上海市科学技术委员会基础研究项目（18JC1414200） |
|
| Construction and in vitro evaluation of a biomimetic nano-delivery system for alleviating hypoxia |
| LI J uan-juan1,GONG Chun-ai2,HAN Zhi-min1,CHEN Xin-lu1,GUO Huan-huan1,GAO Shen1* |
(1. Department of Pharmacy, Changhai Hospital, Naval Medical University (Second Military Medical University), Shanghai 200433, China;
2. Department of Pharmacy, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
*Corresponding author) |
| Abstract: |
| Objective To prepare doxorubicin (Dox)-loaded hollow mesoporous manganese dioxide (H-MnO2) nanoparticles encapsulated with pH-sensitive fusion membrane (MP) (MP@H-MnO2-Dox nanoparticles), and investigate its characteristics in vitro.Methods With solid silica as template, H-MnO2 was synthesized by alkali etching. Dox-loaded H-MnO2 (H-MnO2-Dox) was prepared and was coated with MP to construct MP@H-MnO2-Dox nanoparticles. The particle size, drug loading and proportion of MP coating carriers were investigated, the oxygen production capacity was evaluated by tris(4, 7-diphenyl-1, 10-phenanthroline)ruthenium(Ⅱ) dichloride (RDPP) probe, the drug release in vitro was investigated by dialysis, and the celluar uptake and distribution were investigated by confocal laser scanning microscopy.Results H-MnO2 was successfully prepared. The drug-loading rate and encapsulation efficiency were (79.0±8.7)% and (75.1±7.5)%, respectively. H-MnO2 could be coated well with the mass ratio 1:1 of MP to H-MnO2. The particle size of MP@H-MnO2-Dox nanoparticles was (178.0±9.5) nm. The results of RDPP showed that H-MnO2 possessed superior oxygen production capacity. In vitro drug release results showed that MP could delay Dox release, and the Dox cumulative release amount of MP@H-MnO2-Dox (pH=6.5) was lower than that of H-MnO2-DOX (pH=6.5) ([42.0±5.1]% vs[60.0±3.7]%). The results of uptake experiments showed that MP@H-MnO2-Dox nanoparticles had strong cellular uptake at pH=6.5.Conclusion MP@H-MnO2-Dox nanoparticle is successfully constructed. This biomimetic nanosystem is expected to be a multifunctional drug delivery vehicle for alleviating hypoxia and targeting breast cancer. |
| Key words: hypoxia chemotherapy biomimetic nanoparticles breast neoplasms targeted therapy |
